Genetics of Monogenic Disorders of Calcium and Bone Metabolism

Overview

Journal Clin Endocrinol (Oxf)

Specialty Endocrinology

Date 2021 Dec 22

PMID 34935164

Citations 7

Authors

Paul J Newey

Fadil M Hannan

Abbie Wilson

Rajesh V Thakker

Affiliations

Soon will be listed here.

Abstract

Disorders of calcium homeostasis are the most frequent metabolic bone and mineral disease encountered by endocrinologists. These disorders usually manifest as primary hyperparathyroidism (PHPT) or hypoparathyroidism (HP), which have a monogenic aetiology in 5%-10% of cases, and may occur as an isolated endocrinopathy, or as part of a complex syndrome. The recognition and diagnosis of these disorders is important to facilitate the most appropriate management of the patient, with regard to both the calcium-related phenotype and any associated clinical features, and also to allow the identification of other family members who may be at risk of disease. Genetic testing forms an important tool in the investigation of PHPT and HP patients and is usually reserved for those deemed to be an increased risk of a monogenic disorder. However, identifying those suitable for testing requires a thorough clinical evaluation of the patient, as well as an understanding of the diversity of relevant phenotypes and their genetic basis. This review aims to provide an overview of the genetic basis of monogenic metabolic bone and mineral disorders, primarily focusing on those associated with abnormal calcium homeostasis, and aims to provide a practical guide to the implementation of genetic testing in the clinic.

Citing Articles

Case report: Familial hypoparathyroidism with elevated parathyroid hormone due to an inactivating mutation.

Mukhtar N, Alghamdi B, Alswailem M, Alsagheir A, Alzahrani A Front Endocrinol (Lausanne). 2024; 15:1415639.

PMID: 39435356 PMC: 11491329. DOI: 10.3389/fendo.2024.1415639.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.

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PMID: 38928056 PMC: 11203827. DOI: 10.3390/ijms25126349.

Insights into Hyperparathyroidism-Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of Gene and Parafibromin-Deficient Tumours.

Gheorghe A, Sima O, Florescu A, Ciuche A, Nistor C, Sandru F Int J Mol Sci. 2024; 25(4).

PMID: 38396977 PMC: 10889221. DOI: 10.3390/ijms25042301.

GNA11 Variants Identified in Patients with Hypercalcemia or Hypocalcemia.

Howles S, Gorvin C, Cranston T, Rogers A, Gluck A, Boon H J Bone Miner Res. 2023; 38(6):907-917.

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